This proposed Program-Project affords a confluence of experienced investigators in a highly interacting study of oxygen, energy and contractility in cardiac tissue at three levels. The first deals with the molecular mechanism of the reaction of cytochrome oxidase with oxygen from the kinetic standpoint, with emphasis on the study of intermediates trapped at low temperatures and the thermodynamic and metabolic controls imposed upon this reaction. The second explores the structural-functional aspects of the role of the membrane in oxygen diffusion, in the cytochrome oxidase-oxygen reaction, and in Ca 2 ion transport in the sarcoplasmic reticulum. The third focuses on the bioenergetic activity of cardiac tissue in the sarcoplasmic reticulum, in cultured cardiac cells, and in muscle strips, with emphasis on metabolic regulation. The expression of these various experimental results is then applied to a wide range of biological systems, ranging from the growth the development of cardiac cells in tissue culture, through perfused heart and heart in situ in small animals, to larger animal models with the eventual proposal for clinical trials of the readout of the bioenergetic state and the degree of oxygenation localized in two dimensions on the epicardium and ultimately the endocardium of heart in situ.